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Blocker-SELEX: a structure-guided strategy for developing inhibitory aptamers disrupting undruggable transcription factor interactions

文献类型：期刊论文

作者Li, Tongqing4,5; Liu, Xueying5; Qian, Haifeng5; Zhang, Sheyu3,5; Hou, Yu4,5; Zhang, Yuchao5; Luo, Guoyan5; Zhu, Xun4,5; Tao, Yanxin1,2,5; Fan, Mengyang5
刊名NATURE COMMUNICATIONS
出版日期2024-08-08
卷号15期号:1页码:17
DOI10.1038/s41467-024-51197-w
通讯作者Wei, Yong(weiyong@ibmc.ac.cn) ; Wu, Qin(wuqin@ibmc.ac.cn) ; Tan, Weihong(tan@hnu.edu.cn)
英文摘要Despite the well-established significance of transcription factors (TFs) in pathogenesis, their utilization as pharmacological targets has been limited by the inherent challenges in modulating their protein interactions. The lack of defined small-molecule binding pockets and the nuclear localization of TFs do not favor the use of traditional tools. Aptamers possess large molecular weights, expansive blocking surfaces and efficient cellular internalization, making them compelling tools for modulating TF interactions. Here, we report a structure-guided design strategy called Blocker-SELEX to develop inhibitory aptamers (iAptamers) that selectively block TF interactions. Our approach leads to the discovery of iAptamers that cooperatively disrupt SCAF4/SCAF8-RNAP2 interactions, dysregulating RNAP2-dependent gene expression, which impairs cell proliferation. This approach is further applied to develop iAptamers blocking WDR5-MYC interactions. Overall, our study highlights the potential of iAptamers in disrupting pathogenic TF interactions, implicating their potential utility in studying the biological functions of TF interactions and in nucleic acids drug discovery. Transcription factors are crucial in disease but hard to target with traditional drugs. Here, authors present BlockerSELEX, a strategy to develop inhibitory aptamers that block transcription factor interactions, which disrupts interactions between key proteins, showing potential for new nucleic acid therapies.
WOS关键词RNA APTAMER ; PROTEIN ; BINDING ; DOCKING ; OPTIMIZATION ; COMPLEX
资助项目National Natural Science Foundation of China (National Science Foundation of China)[2022YFC3400400] ; National Key R&D Program of China[32201010] ; National Key R&D Program of China[82103287] ; National Key R&D Program of China[YQ2022HW01] ; National Natural Science Foundation of China[LR22B050001] ; National Natural Science Foundation of China[2023SDYXS0003] ; National Natural Science Foundation of China[YXD24B0701] ; National Natural Science Foundation of China[2023SDYXS0002] ; Zhejiang Provincial Natural Science Foundation of China[ZJ2022048] ; Zhejiang Province Postdoctoral Research Project Merit-based Funding Project
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001287600900024
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/312881]  
专题中国科学院上海药物研究所
通讯作者Wei, Yong; Wu, Qin; Tan, Weihong
作者单位1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
3.Tianjin Univ, Sch Life Sci, Tianjin, Peoples R China
4.Zhejiang Univ Technol, Sch Pharm, Hangzhou, Peoples R China
5.Chinese Acad Sci, Hangzhou Inst Med, Hangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Li, Tongqing,Liu, Xueying,Qian, Haifeng,et al. Blocker-SELEX: a structure-guided strategy for developing inhibitory aptamers disrupting undruggable transcription factor interactions[J]. NATURE COMMUNICATIONS,2024,15(1):17.
APA Li, Tongqing.,Liu, Xueying.,Qian, Haifeng.,Zhang, Sheyu.,Hou, Yu.,...&Tan, Weihong.(2024).Blocker-SELEX: a structure-guided strategy for developing inhibitory aptamers disrupting undruggable transcription factor interactions.NATURE COMMUNICATIONS,15(1),17.
MLA Li, Tongqing,et al."Blocker-SELEX: a structure-guided strategy for developing inhibitory aptamers disrupting undruggable transcription factor interactions".NATURE COMMUNICATIONS 15.1(2024):17.

入库方式： OAI收割

来源：上海药物研究所

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